全文获取类型
收费全文 | 102篇 |
免费 | 5篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 6篇 |
妇产科学 | 4篇 |
基础医学 | 23篇 |
口腔科学 | 4篇 |
临床医学 | 2篇 |
内科学 | 17篇 |
神经病学 | 10篇 |
外科学 | 7篇 |
综合类 | 1篇 |
预防医学 | 1篇 |
眼科学 | 6篇 |
药学 | 3篇 |
肿瘤学 | 20篇 |
出版年
2023年 | 4篇 |
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 8篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2014年 | 5篇 |
2013年 | 5篇 |
2012年 | 5篇 |
2011年 | 10篇 |
2010年 | 5篇 |
2009年 | 3篇 |
2008年 | 10篇 |
2007年 | 6篇 |
2006年 | 3篇 |
2005年 | 6篇 |
2004年 | 5篇 |
2003年 | 4篇 |
2001年 | 1篇 |
排序方式: 共有108条查询结果,搜索用时 0 毫秒
1.
Mathur SR Dahiya S Nayak A Bhatla N Singh MK 《Indian journal of pathology & microbiology》2004,47(3):333-335
We describe the clinicopathological and immunohistochemical findings in five cases of sclerosing stromal tumours of ovary and compare our findings with other reported cases of this uncommon tumour and with fibromas and thecomas which they may mimic. 相似文献
2.
Ujjwal Sonika Shekhar Jadaun Gyan Ranjan Gyanranjan Rout Deepak Gunjan Saurabh Kedia Baibaswata Nayak Shalimar 《Indian journal of gastroenterology》2018,37(1):50-57
Background and Aims
Various prognostic scores are available for predicting outcome in acute-on-chronic liver failure (ACLF). We compared the available prognostic models as predictors of outcome in alcohol-related ACLF patients.Methods
All consecutive patients with alcohol-related ACLF were included. At admission, prognostic indices-acute physiology and chronic health evaluation score (APACHE II), model for end-stage liver disease (MELD), MELD-Na, Maddrey’s discriminant function (DF), age-bilirubin-INR-creatinine (ABIC), and Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C ACLF) score were calculated. Receiver operator characteristic (ROC) curves were plotted for all prognostic scores with in-hospital, 90-day, and 1-year mortality as outcome.Results
Of the 171 patients, 170 were males, and grade 1 ACLF in 20 (11.7%), grade 2 in 52 (30.4%), and grade 3 in 99 (57.9%) patients. One hundred and nineteen (69.6%) died in-hospital. The median (IQR) Maddrey’s score, MELD, MELD-Na, ABIC, APACHE II, and CLIF-C ACLF were 87.8 (66.5–123.0), 33.1 (27.6–40.0), 34.4 (29.5–40.0), 8.5 (7.3–9.6), 15 (12–21), and 51.1 (44.1–56.4), respectively. On multivariate Cox regression analysis, independent predictors of in-hospital outcome were presence of hepatic encephalopathy (early HR, 2.078; 95%CI, 1.173–3.682, p?=?0.012 and advanced, HR, 2.330; 95% CI, 1.270–4.276, p?=?0.006), elevated serum creatinine (HR, 1.140; 95% CI, 1.023–1.270, p?=?0.018), and infection at admission (HR, 1.874; 95% CI, 1.160–23.029, p?=?0.010). On comparison of ROC curves, APACHE II and CLIF-C ACLF AUROC were significantly higher than MELD, MELD-Na, DF, and ABIC (p?<?0.05) for predicting in-hospital, 90-day, and 1-year mortality. The AUROC was highest for APACHE II followed by CLIF-C ACLF (Hanley and McNeil, p?=?0.660).Conclusions
Alcohol-related ACLF has high in-hospital mortality. Among the available prognostic scores, CLIF-C ACLF and APACHE II perform best.3.
Aseem Lal Sonika Dahiya Michael Gonzales Annie Hiniker Richard Prayson Bette K. Kleinschmidt‐DeMasters Arie Perry 《Brain pathology (Zurich, Switzerland)》2014,24(4):352-359
Meningiomas with prominent inflammation are traditionally classified as “lymphoplasmacyte‐rich meningioma” (LPM). Both inflammatory and neoplastic meningeal proliferations have recently been linked to IgG4 disease, although a potential association with LPM has not been previously explored. Sixteen meningiomas with inflammatory cells outnumbering tumor cells were further characterized by CD3, CD20, CD68 and/or CD163, CD138, kappa, lambda, IgG and IgG4 immunostains. There were 11 female and 4 male patients, ranging from 22 to 78 (median 59) years of age. Tumors consisted of 10 World Health Organization (WHO) grade I, 5 grade II and 1 grade III LPMs. Immunohistochemically, the most numerous cell type was the macrophage in all cases followed by CD3‐positive T cells and fewer CD20‐positive B cells. Plasma cells ranged from moderate‐marked (N = 5) to rare (N = 7), or absent (N = 4). Maximal numbers of IgG4 plasma cells per high power field (HPF) ranged from 0 to 32, with only two cases having counts exceeding 10/HPF. The IgG4/IgG ratio was increased focally in only two cases (30% and 31%). Additionally, plasma cells represented only a minor component in most examples, whereas macrophages predominated, suggesting that “inflammation‐rich meningioma” may be a more accurate term. The inflammatory stimulus for most cases remains to be elucidated. 相似文献
4.
Leo H. Wang Robert C. Bucelli Erica Patrick Dhanashree Rajderkar Enrique Alvarez III Miranda M. Lim Gabriela DeBruin Victoria Sharma Sonika Dahiya Robert E. Schmidt Tammie S. Benzinger Beth A. Ward Beau M. Ances 《Journal of neurology》2013,260(2):498-506
Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive dementia (RPD) that can be difficult to identify antemortem, with definitive diagnosis requiring tissue confirmation. We describe the clinical, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and electroencephalogram (EEG) measures of a small cohort of 30 patients evaluated for RPD. Clinical and diagnostic measures were cross-sectionally obtained from 17 sCJD patients (15 definite, two probable), 13 non-prion rapidly progressive dementia patients (npRPD), and 18 unimpaired controls. In a subset of patients (nine sCJD and nine npRPD) diffusion tensor imaging (DTI) measures [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)] were also obtained for the caudate, corpus callosum, posterior limb of the internal capsule, pulvinar, precuneus, and frontal lobe. Differences among groups were assessed by an analysis of variance. Compared to npRPD individuals, sCJD patients had cerebellar dysfunction, significantly higher CSF tau, “positive” CSF 14-3-3, and hyperintensities on diffusion-weighted imaging (DWI) that met previously established imaging criteria for sCJD. EEG changes were similar for the two groups. In addition, sCJD patients had significant decreases in DTI measures (MD, AD, RD but not FA) within the caudate and pulvinar compared to either npRPD patients or unimpaired controls. Our results confirm that CSF abnormalities and MRI (especially DWI) can assist in distinguishing sCJD patients from npRPD patients. Future longitudinal studies using multiple measures (including CSF and MRI) are needed for evaluating pathological changes seen in sCJD patients. 相似文献
5.
Pankaj Kumar Singh Sonika Chibh Taru Dube Virander Singh Chauhan Jiban Jyoti Panda 《Pharmaceutical research》2018,35(2):35
Purpose
Nanoparticles (NPs) exhibiting responsiveness towards pH variations in organs, tissue microenvironments and cellular compartments can significantly add on to the drug delivery potential. Here, we have developed NPs from an amphipathic dipeptide, Arginine-α, β-dehydrophenylalanine (RΔF), and tried to explore their pH responsive drug delivery potential in various cancer cells.Methods
RΔF-NPs were architectured by harnessing the process of molecular self-assembly followed by the assessment of effect of pH on NPs morphology using zetasizer, SEM and CD. FTIR and PXRD analysis of the dipeptide and doxorubicin (Dox) were carried out for compatibility assessment followed by encapsulation of Dox in RΔF-NPs. RΔF-Dox-NPs were evaluated for pH dependent release as well as for in-vitro cellular internalization and efficacy in cancer cells.Results
RΔF self-assembled to form monodispersed particles at pH 7. SEM analysis revealed a loss of overall particle morphology along with particle aggregation at highly acidic and basic pH respectively. The NPs demonstrated a slow and sustained release behaviour at pH 7 (97.64?±?4.71% after 36 h) in comparison to pH 2 (90.27?±?1.45% after 8 h) and pH 10 (96.39?±?3.87% after 12 h). In-vitro efficacy studies carried-out in various cancer cells revealed that RΔF-Dox-NPs exhibited higher efficacy with 1.65, 1.95 and 13.34 fold lower IC50 values in comparison to Dox in C6, HCT-116 and AGS cell lines.Conclusions
RΔF-Dox-NPs with higher drug release at acidic pH, enhanced internalization in cancer cells along with higher cytotoxic potential can act as effective pH responsive drug delivery systems.6.
Lin Alexander J. Kane Liam T. Molitoris Jason K. Smith Deborah R. Dahiya Sonika Badiyan Shahed N. Wang Tony J. C. Kruser Tim J. Huang Jiayi 《Journal of neuro-oncology》2020,146(1):121-130
Journal of Neuro-Oncology - Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage... 相似文献
7.
Miles A. Miller Aaron S. Meyer Michael T. Beste Zainab Lasisi Sonika Reddy Karen W. Jeng Chia-Hung Chen Jongyoon Han Keith Isaacson Linda G. Griffith Douglas A. Lauffenburger 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(22):E2074-E2083
A Disintegrin and Metalloproteinases (ADAMs) are the principal enzymes for shedding receptor tyrosine kinase (RTK) ectodomains and ligands from the cell surface. Multiple layers of activity regulation, feedback, and catalytic promiscuity impede our understanding of context-dependent ADAM “sheddase” function and our ability to predictably target that function in disease. This study uses combined measurement and computational modeling to examine how various growth factor environments influence sheddase activity and cell migration in the invasive disease of endometriosis. We find that ADAM-10 and -17 dynamically integrate numerous signaling pathways to direct cell motility. Data-driven modeling reveals that induced cell migration is a quantitative function of positive feedback through EGF ligand release and negative feedback through RTK shedding. Although sheddase inhibition prevents autocrine ligand shedding and resultant EGF receptor transactivation, it also leads to an accumulation of phosphorylated receptors (HER2, HER4, and MET) on the cell surface, which subsequently enhances Jnk/p38 signaling. Jnk/p38 inhibition reduces cell migration by blocking sheddase activity while additionally preventing the compensatory signaling from accumulated RTKs. In contrast, Mek inhibition reduces ADAM-10 and -17 activities but fails to inhibit compensatory signaling from accumulated RTKs, which actually enhances cell motility in some contexts. Thus, here we present a sheddase-based mechanism of rapidly acquired resistance to Mek inhibition through reduced RTK shedding that can be overcome with rationally directed combination inhibitor treatment. We investigate the clinical relevance of these findings using targeted proteomics of peritoneal fluid from endometriosis patients and find growth-factor–driven ADAM-10 activity and MET shedding are jointly dysregulated with disease.A Disintegrin and Metalloproteinases (ADAMs), especially ADAM-10 and -17, are the principal mediators of proteolytic ectodomain shedding on the cell surface (1). ADAMs and the closely related matrix metalloproteinases (MMPs) work together as “sheddases” to cleave hundreds of diverse transmembrane substrates including growth factor ligands, receptor tyrosine kinases (RTKs), adhesion molecules, and even proteases themselves from the cell surface. Unfortunately, little is known regarding how such a broad palette of proteolytic activity integrates to modulate behaviors such as cellular motility. Furthermore, extensive cross-talk and complexity among signaling networks, proteases, and their substrates make understanding sheddase regulation on a component-by-component basis challenging (2). Therapeutics have targeted sheddases and their substrates for the treatment of invasive diseases such as cancer, yet many of these inhibitors have failed in clinical trials (3). Therefore, a need exists for understanding how the balance of sheddase-mediated degradation integrates multiple layers of signaling networks to coordinately influence cell behavior in various disease contexts.Here we study how sheddase activity contributes to cell migration in the invasive disease of endometriosis, defined by the presence of endometrial-like tissue residing outside the uterus. Up to 10% of adult females and 40% of infertile women have the disease, which also exhibits comorbidity with several cancers (4, 5). Endometriosis currently has no cure: hormonal therapies merely manage the disease with significant side effects, and surgery provides only temporary relief for many, with recurrence rates as great as 40% within 5 y postoperation (6). Like cancer, endometriosis is associated with aberrant cell invasion into ectopic organ sites, and endometriotic tissues often exhibit dysregulated molecular pathways commonly perturbed in other invasive diseases. Mitogenic and inflammatory phospho-signaling [for example, phosphorylated extracellular-signal-related kinase 1/2 (p-Erk1/2), phosphorylated protein kinase B (p-Akt), and phosphorylated p38 mitogen-activated protein kinase (p-p38)], RTKs (including epidermal growth factor receptor, EGFR), and metalloproteinases have all been clinically associated with endometriosis (7, 8), and consequently represent attractive therapeutic strategies (9–11).Many challenges in developing targeted therapeutics stem from network-level complexities such as compensatory feedback, and recent work has demonstrated how critical such mechanisms are to achieving therapeutic success, especially in cancer (12, 13). Computational models of systems-level biochemical networks have shown promise as tools to understand how multiple enzymatic reactions integrate to impact overall biological behavior, often with the goal of aiding the design of personalized or combination therapies (14, 15). Considering its complex role in disease, sheddase regulation represents an ideal application of such network-level approaches. In this work, we apply the “cue–signal–response” (CSR) paradigm (14, 15) (Fig. 1A) to examine how disease-implicated growth-factor cues interact with experimentally monitored phospho-protein and protease networks (collectively referred to as signals), ultimately to influence cellular migration response. Computational modeling elucidates quantitative and predictive relationships among multiple layers of experimental data and offers testable hypotheses of context-dependent behavior and signaling feedback. We find ADAM-10 and -17 to be critical regulators of motility that are dynamically controlled through several signaling pathways, thereby affecting cell behavior through both positive feedback from EGF ligand release and negative feedback from Hepatocyte Growth Factor Receptor (HGFR; MET), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4 RTK shedding. We find kinase inhibition generally reduces ADAM-10 and -17 activities, reduces subsequent RTK shedding, and consequently allows the accumulated RTKs to enhance downstream c-Jun N-terminal kinase (Jnk) and p38 signaling. Thus, here we demonstrate an ADAM-10 and -17–based mechanism of rapidly acquired resistance to kinase inhibition through reduced RTK shedding that can be overcome with combination therapy. Targeted proteomic analysis of clinical samples from endometriosis patients indeed confirms growth-factor–driven ADAM-10 activity and consequent MET shedding are dysregulated with disease. Overall, our results have wide implications for designing combination therapies and identifying context-dependent personalized therapeutic strategies for both kinase and protease inhibitors.Open in a separate windowFig. 1.CSR study design. (A) CSR overview: we stimulate endometriotic cells with a panel of growth factor cues; record multiple downstream signals comprising measurements of phospho-signaling, sheddase regulation, and sheddase substrate regulation; and use computational modeling to map these observations onto cell migration responses. (B) Overview of signals and responses included in the CSR dataset. All receptors shown were directly measured and/or stimulated. (C) Experimental timeline of CSR study. Dark colored lines denote measurement time points. At lower left, cell migration is depicted as single-cell tracks, where initial cell positions were centered for visualization. 相似文献
8.
Alok Thakar Chitra Sarkar Muthuswamy Dhiwakar Sudhir Bahadur Sonika Dahiya 《Otolaryngology--head and neck surgery》2004,130(2):209-216
OBJECTIVE: We sought to determine whether histologic tissue invasion occurs in allergic fungal sinusitis (AFS) and, if so, to identify clinical indicators for the same.Study design and setting We conducted a retrospective case record review of all 28 AFS cases identified by histology over a 32-month period at a tertiary care referral center. All histologic specimens were reevaluated for features of invasive pathology, and case records were correlated for clinical, radiologic, or laboratory parameters associated with such invasion. RESULTS: In addition to the universal finding of the characteristic allergic mucin with fungal elements on histopathologic examination of the sinus luminal contents, 6 cases (21%) had additional evidence of mucosal invasion as indicated by granulomatous inflammation and branching septate fungal hyphae in the submucosal tissues. Such coexistent invasion was associated with advanced disease as indicated by a higher incidence of orbital involvement on clinical evaluation (P = 0.024), and extrasinus spread (intraorbital or intracranial spread) on the computed tomography evaluation (P = 0.003). The single death that occurred on follow-up was in a patient with coexistent invasion. CONCLUSION: Advanced AFS may be complicated by histologic evidence of tissue invasion. SIGNIFICANCE: The noninvasive and invasive forms of fungal sinusitis are not necessarily discrete and may coexist in the same patient. Clinical features of orbital involvement or computed tomography manifestations of extrasinus spread should alert the clinician to the possibility of invasion. 相似文献
9.
Objective: Diagnosis of childhood tuberculosis remains an enigma despite many recent technological developments. The present study
has been taken up with the aim to assess the diagnostic potential of mycobacterium tuberculosis excretory-secretory ES-31
antigen and affinity purified anti ES-31 antibodies in the serodiagnosis of different spectrum of childhood tuberculosis.Methods: Mycobacterium tuberculosis H37 Ra excretory-secretory antigen (ES-31) and affinity purified goat anti ES-31 antibodies were used in stick penicillinase
ELISA for IgG antibody detection and stick Sandwich penicillinase ELISA for detection of circulating free and immune complexed
antigen in the sera of 230 children.Results: Analysis of tubercular antibody, circulating free and immune complexed antigen (CIC-Ag) was done in both pulmonary and extrapulmonary
form of childhood tuberculosis and overall sensitivity of 81.4% with a specificity of 93% was achieved for detection of antitubercular
IgG antibodies. Of the five cases of pulmonary tuberculosis showing absence of IgG antibody, 3 showed the presence of CIC-Ag
and one was found positive for both free and CIC-Ag. Similarly out of 8 cases of extrapulmonary childhood tuberculosis missed
by IgG detection 5 were found to be positive for CIC-Ag and 1 showed the positive reaction for both free and immune complexed
antigens.Conclusion: IgG antibody to excretory-secretory antigen ES-31 is found to be having good specificity with acceptable sensitivity in
detecting different forms of childhood tuberculosis. Further detection of circulating free and / or immunecomplexed antigen
can be used as an adjunct tool in the diagnosis of childhood tuberculosis. 相似文献
10.
Posterior scleritis mimicking macular serpiginous choroiditis 总被引:1,自引:0,他引:1
Sonika Narang S Kochhar S Srivastava M Gupta R Sood S 《Indian journal of ophthalmology》2003,51(4):351-353
An unusual case of posterior scleritis mimicking macular serpiginous choroiditis is reported. 相似文献